Exposure of the skin to environmental antigens can lead to generation of either Th1 or Th2 type immune responses. The recent demonstration that epicutaneous exposure of mice to soluble protein results in preferential activation of Th2 effector cells has provided a novel animal model of epicutaneously induced Th2 immune responses. The proposed studies involve investigation of the immunoregulatory factors controlling recruitment of inflammatory cells to the skin in mice epicutaneously exposed to soluble protein. Preliminary studies of lung inflammatory responses induced by airway challenge of epicutaneously sensitized mice have revealed an interesting difference in the IL-4 dependence of these responses between different mouse strains. While epicutaneous exposure to ovalbumin (OVA) resulted in markedly skewed Th2 responses in both BALB/c and C57BL/6 mice, a difference emerged between these two strains of mice following intranasal challenge of epicutaneously sensitized IL deficient (IL -/-) mice. Specifically, C57BLI6 mice, but not BALB/c mice, possess an IL-4 independent mechanism for recruitment of eosinophils to the airway. However, airway eosinophi1ia in C57BL/6 mice is STAT6 (signal transducer and activator of transcription factor 6) dependent, implicating IL-13 as the critical factor in recruitment of eosinophils to the airway. The goal of this pilot study is to determine whether a similar strain difference exists with regard to control of inflammatory responses in the skin following epicutaneous sensitization with protein. In particular, is the recruitment of eosinophils to the skin IL-4 dependent in BALB/c mice, but IL-4 independent in C57BL/6 mice, and what role does IL-13 play in generation of skin inflammation? These questions will be addressed by: 1) Characterization of inflammatory responses induced in the skin of epicutaneously immunized BALB/c and C57BL/6 mice; and 2) Definition of the role of IL-13 in cutaneous inflammatory responses. This data will provide valuable information regarding the pathogenesis of certain dermatologic conditions triggered by cutaneous exposure to protein antigens, such as allergic contact urticaria and latex hypersensitivity reactions, and may also yield new insight into other skin diseases thought to involve Th2 activation, such as atopic dermatitis. Establishment of this novel model of Th2-mediated cutaneous inflammatory responses in mice will provide a means for future investigation of the immunoregulatory factors operating in the cutaneous microenvironment.